I. To estimate the frequency and severity of toxicities of the intensive short-term
chemotherapy regimen in these patients.

II. To estimate the overall survival of all patients on this study.

OUTLINE: This is a multicenter study.

Patients are stratified according to prior treatment and response (untreated vs achieved
complete remission [CR] with or without [CRi] hematopoietic recovery vs treated, refractory,
and no CR or CRi).

INDUCTION/CONSOLIDATION THERAPY: All patients receive both of the following regimens in
alternating courses:

COURSES 1, 3, 5, 7 or 3, 5, 7, 9: Patients receive cyclophosphamide intravenously (IV) over
3 hours twice daily (BID) on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4;
vincristine sulfate IV over 30 minutes on days 4 and 11; dexamethasone IV or orally (PO)
once daily (QD) on days 1-4 and 11-14; dasatinib PO QD on days 1-14; cytarabine
intrathecally (IT) on day 7; methotrexate IT on day 2; and filgrastim (G-CSF) subcutaneously
(SC) QD or BID.

COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 24 hours on day 1;
methylprednisolone IV over 30 minutes BID on days 1-3; dasatinib PO QD on days 1-14;
high-dose cytarabine IV over 2 hours BID on days 2-3; leucovorin calcium IV on days 2 or 3;
methotrexate IT on day 2; cytarabine IT on day 7; and G-CSF SC QD or BID.

Treatment repeats every 14-21 days for 8 courses in the absence of disease progression,
unacceptable toxicity, or if patient achieves CR or CRi.

MAINTENANCE THERAPY*: Patients receive vincristine sulfate IV over 30 minutes on day 1,
prednisone PO QD on days 1-5, and dasatinib PO QD on days 1-28.

Treatment repeats every month for 24 courses in the absence of disease progression or
unacceptable toxicity or until the transplant is ready.

INTENSIFICATION: For courses 6 and 13, patients receive cyclophosphamide IV over 3 hours BID
on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV
over 30 minutes on days 4 and 11; dexamethasone IV or PO QD on days 1-4 and 11-14; dasatinib
PO QD on days 1-14; and G-CSF SC QD or BID.

NOTE: *Only if transplantation is not ready after induction/consolidation therapy or
patients are not undergoing a transplant.

SINGLE-AGENT THERAPY: After completion of maintenance therapy or beginning on day 100
post-transplantation, patients receive dasatinib PO QD for up to 5 years.

Bone marrow and blood samples are collected periodically for cytogenetic analysis by PCR and
flow cytometry.

After completion of study therapy, patients are followed every 6 months for up to 5 years.

Inclusion Criteria:

- Patients must have a morphologic diagnosis of acute lymphoblastic leukemia (ALL),
with evidence of ALL involvement in bone marrow and/or blood; patients with only
extramedullary disease in the absence of bone marrow or blood involvement are not
eligible; patients with M0 acute myeloid leukemia (AML) or mixed lineage leukemia are
not eligible for this study; patients with L3 (Burkitts) are also not eligible

- For ALL in marrow or peripheral blood, immunophenotyping of the blood or marrow
lymphoblasts must be performed to determine lineage (B cell, T-cell, or mixed
B/T cell); NOTE: appropriate marker studies including CD19 (B cell), CD10, CD5,
and CD7 (T cell) must be performed; co-expression of myeloid antigens (CD13 and
CD33) will not exclude patients; if possible, the lineage specific markers
cytoplasmic CD22 or CD79a (B cells), cytoplasmic CD3 (T cells) and cytoplasmic
MPO (myeloid cells) must be determined

- Patients may have received no more than one course of remission induction therapy for
ALL; patients who have received any post-remission therapy for ALL or who have
relapsed from complete remission are not eligible; (patients with previously
untreated ALL can be eligible, and patients who have received one course of remission
induction therapy for ALL can be eligible, regardless of their response to therapy);
patients may have received no more than 14 days of tyrosine kinase inhibitor therapy
prior to registration; any prior induction chemotherapy must have been completed no
more than 28 days prior to registration

- NOTE: If the patient has been initiated on the protocol defined regimen (i.e.
the hyperCVAD regimen without a tyrosine kinase inhibitor) before the
Philadelphia chromosome (Ph)/breakpoint cluster region (BCR)-Abelson murine
leukemia viral oncogene (ABL) status was known, the patient may be registered on
the protocol and start dasatinib; in this first course, dasatinib will be
administered up to day 14 (i.e. if the patient is registered on day 5 and starts
therapy on day 6, only 8 days of dasatinib will be administered and dasatinib
will be completed on day 14)

- For patients who have received any prior therapy that was NOT remission induction
therapy, one of the following must be true:

- At least 6 weeks must have elapsed since any monoclonal antibodies were given,
at least 7 days must have elapsed since any other treatment was given, and all
toxicities of the remission induction therapy must have resolved to grade =< 2

- For previously treated patients, the Study Chair must be contacted before
registration, in order to determine the regimen to be given in the first course of
induction/consolidation therapy, based on prior therapy

- Patients must be Ph positive and/or BCR/ABL positive as confirmed by standard
cytogenetics, fluorescent in situ hybridization (FISH), and/or polymerase chain
reaction (PCR) testing performed by local laboratory; NOTE: samples will be submitted
centrally for verification of results

- Patients must have a bilirubin =< 3.0 x institutional upper limit of normal (IULN)
within 14 days prior to registration

- Patients must have a serum creatinine =< 3.0 x IULN within 14 days prior to
registration

- Patients must not have active pericardial effusion, ascites, or pleural effusion of
any grade; exception: if the effusion is suspected to be related to the leukemia, the
patient may have pericardial effusion of =< grade 2 or pleural effusion =< grade 1

- Patients may not have any clinically significant cardiovascular disease including the
following:

- Major conduction abnormality (unless a cardiac pacemaker is present)

- Patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of
breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with
or without stress test as needed in addition to electrocardiogram (EKG) to rule
out QTc prolongation; the patient may be referred to a cardiologist at the
discretion of the principal investigator; patients with underlying
cardiopulmonary dysfunction should be excluded from the study

- Patients must have Zubrod performance status of 0-2

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
stage I or II cancer from which the patient is currently in complete remission, or
any other cancer from which the patient has been disease-free for 5 years

- Collection and submission of pre-treatment cytogenetic specimens must be completed
within 28 days prior to registration on S0805

- Collection and submission of pretreatment marrow and/or peripheral blood specimens
for cellular and molecular studies, including verification of BCR/ABL status must be
completed within 28 days prior to registration

- Patients must not be pregnant or nursing because of the teratogenic potential of the
drugs used in this study; women/men of reproductive potential must have agreed to use
an effective contraceptive method; a woman is considered to be of "reproductive
potential" if she has had menses at any time in the preceding 12 consecutive months;
in addition to routine contraceptive methods, "effective contraception" also includes
heterosexual celibacy and surgery intended to prevent pregnancy (or with a
side-effect of pregnancy prevention) defined as a hysterectomy, bilateral
oophorectomy or bilateral tubal ligation; however, if at any point a previously
celibate patient chooses to become heterosexually active during the time period for
use of contraceptive measures outlined in the protocol, he/she is responsible for
beginning contraceptive measures

- Patients must not have prior history of known type I hypersensitivity or anaphylactic
reactions to doxorubicin

- Patients or their legally authorized representative must be informed of the
investigational nature of this study and must sign and give written informed consent
in accordance with institutional and federal guidelines

- At the time of patient registration, the treating institution's name and
identification (ID) number must be provided to the Data Operations Center in Seattle
in order to ensure that the current (within 365 days) date of institutional review
board approval for this study has been entered into the data base

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